Ulceration, fibrosis and diaphragm-like lesions in the caecum of rats treated with indomethacin

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Abstract
Patients on nonsteroidal anti-inflammatory drugs can develop curious intestinal fibrotic diaphragms. Groups of rats received indomethacin mixed into a powdered diet at 3 mg.kg/day for 6 and 12 weeks and 6 mg.kg/day for up to 6 weeks. In an attempt to reproduce a human dosing regimen, another group of rats, for a total of 30 weeks, received consecutive periods of indomethacin at 3 mg.kg/day for 12 weeks, 4.5 mg.kg/day for 1 week, 6 mg.kg/day for 1 week, control diet for 6 weeks, 4.5 mg.kg/day for 2 weeks and finally, a control diet for a healing period of 8 weeks. Control rats received powdered diet alone. At termination, the small and large intestines were examined macroscopically and histologically. Indomethacin caused microcytic anaemia, hypoalbuminaemia, small intestinal ulceration, caecal ulceration and inconspicuous raised mucosal lesions in the caecum that histologically showed submucosal fibrosis with disruption and thickening of the apical muscularis mucosae. No control rats showed any abnormality. These fibrotic lesions of the rat caecum resemble human diaphragms and may arise from healed caecal ulcers.